Breast cancer research and treatment
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Breast Cancer Res. Treat. · Jan 2003
ReviewThree years' follow-up from the ATAC trial is sufficient to change clinical practice: a debate.
Tamoxifen is currently the adjuvant treatment of choice for postmenopausal women with hormone-sensitive breast cancer. However, in the treatment of postmenopausal women with advanced disease, the third-generation aromatase inhibitor anastrozole ('Arimidex') has been shown to be at least as effective as tamoxifen, and to be more effective than tamoxifen in patients with estrogen receptor-positive disease. Furthermore, anastrozole is well tolerated and is associated with fewer adverse reactions (such as thromboembolic events, vaginal bleeding, and endometrial cancer) compared with tamoxifen. ⋯ Of course, a large body of evidence is available regarding the safety profile of tamoxifen and some feel that more data are needed from the ATAC trial to demonstrate that the early advantages of anastrozole over tamoxifen can be maintained in the longer term. However, a follow-up analysis at 47 months has confirmed that the tolerability profile and the absolute benefit of anastrozole were maintained over the extended follow-up period, demonstrating that the benefits of anastrozole are likely to be maintained over the long term. This review assesses these and other data from the ATAC trial and presents the arguments for and against whether 3 years' follow-up is sufficient to inform a change in clinical practice for the adjuvant treatment of postmenopausal women with early breast cancer.
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Breast Cancer Res. Treat. · Jan 2003
ReviewThe role of taxanes in the adjuvant treatment of early stage breast cancer.
Adjuvant chemotherapy plays a significant incremental role in improving survival in patients with early stage breast cancer. Survival benefits gained in the adjuvant setting with anthracycline-based polychemotherapy regimens are now level- 1 evidence based, and in an attempt to further these gains, many randomized trials are examining new treatment options. Other important goals include defining the magnitude of benefit with current and investigational regimens in prospectively defined risk groups. ⋯ Only one of the paclitaxel trials so far demonstrated a statistically significant improvement in disease-free and overall survival relative to the comparator, while a second trial demonstrated superiority of dose-dense chemotherapy over conventional dosing. Interim results with docetaxel suggest that substituting docetaxel for fluorouracil in combination with doxorubicin and cyclophosphamide results in improved disease-free survival, with a trend toward improved overall survival. Completion of ongoing trials and maturation of the current data will further define the role of taxanes in the adjuvant treatment of early stage breast cancer.
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Data from the 'Arimidex', Tamoxifen, Alone or in Combination (ATAC) trial have indicated that anastrozole ('Arimidex') may supplant tamoxifen as the preferred adjuvant endocrine therapy for hormone receptor-positive, early breast cancer in postmenopausal women. The acceptability of this change in clinical practice at this time is currently under debate, and depends upon how confident we can be that 4 years' follow-up is sufficient to allow the overall risk:benefit balance to be assessed. The data supporting the benefits of sequential endocrine therapy are more certain, and if anastrozole does become the adjuvant agent of choice, the optimal sequence of endocrine agents will need to be identified for use after recurrence on anastrozole for early disease. ⋯ This has emphasized the importance of understanding the interactions between the different cell-signaling pathways that underlie the development of endocrine resistance. This will present a range of new opportunities for therapeutic intervention and will provide the foundation for the rational design of clinical trials. The resulting incorporation of more target-oriented approaches and newer endocrine agents into the treatment of breast cancer should stimulate the development of promising treatment paradigms and will ultimately provide further benefit to patients.
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Breast Cancer Res. Treat. · Jan 2003
ReviewSequential hormonal therapy for metastatic breast cancer after adjuvant tamoxifen or anastrozole.
The use of adjuvant endocrine therapy in the treatment of hormone receptor-positive, early breast cancer has become important in both pre- and postmenopausal women. Tamoxifen has been the principal adjuvant hormonal therapy in pre- and postmenopausal women with hormone receptor-positive breast cancer for nearly 20 years. Recent data in premenopausal women suggest benefit from ovarian ablation with or without tamoxifen. ⋯ In addition, data suggest that fulvestrant ('Faslodex'), a novel estrogen receptor (ER) antagonist that downregulates the ER protein and has no known agonist effects, is a promising therapeutic option that has shown efficacy in the treatment of postmenopausal women with advanced breast cancer. Other agents that may be used in the sequence include the steroidal AI exemestane and the progestin megestrol acetate. The widening range of adjuvant endocrine options therefore represents an opportunity to prolong patient benefits in the treatment of hormone receptor-positive breast cancer, and will require the further refinement of the optimal sequence of endocrine agents for the treatment of recurrent breast cancer.
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Breast Cancer Res. Treat. · Apr 2002
Comparative StudyHysteroscopic assessment of menopausal breast-cancer patients taking tamoxifen; there is a bias from the mode of endometrial sampling in estimating endometrial morbidity?
The aim of this study is to evaluate the accuracy of hysteroscopy in detecting tamoxifen-associated endometrial morbidity. Ninety-eight menopausal breast cancer patients taking tamoxifen underwent hysteroscopy because of an endometrial thickness above 4mm measured by Transvaginal Ultrasonography. Thirty-one women recorded uterine bleeding while 67 were asymptomatic. ⋯ From literature data, the detection-rate of endometrial pathology in tamoxifen users varies from the lowest to the highest prevalences whether blind or hysteroscopically-targeted modalities of tissue sampling were used, respectively. Hysteroscopy with targeted sampling appears to be the most effective method to assess the endometrial lining. In our experience it is safe, well tolerated and it should be considered the reference test to assess a thickened endometrium in women under tamoxifen.